Toxic Effects of Sorafenib in Patients With Differentiated Thyroid Carcinoma Compared With Other Cancers

IMPORTANCE Sorafenib is approved by the US Food and Drug Administration for metastatic, radioactive iodine-refractory differentiated thyroid cancer. However, adverse effects common to the tyrosine kinase inhibitor class occur at a noticeably higher rate with sorafenib use in thyroid cancer patients. The mechanism for this increase in toxic effects is unknown. OBJECTIVE To provide an overview of the adverse effect profile of sorafenib in differentiated thyroid cancer and summarizes the literature regarding the frequency and etiology of selected adverse effects, with particular emphasis on the hand-foot skin reaction. EVIDENCE REVIEW A PubMed database search for relevant literature on this topic published within the last 15 years was conducted. Publications dealing with sorafenib and any of its common adverse effects were considered; this included randomized trials, observational studies, case reports or case series, and pertinent review articles. Given the lack of widespread literature on the topic, articles were generally not excluded from consideration unless there were serious flaws in study design. FINDINGS The DECISION trial of sorafenib in patients with differentiated thyroid cancer demonstrated significantly higher rates of common adverse effects, most notably hand-foot skin reaction, diarrhea, and hypertension, compared with sorafenib experience in renal or hepatocellular cancer. Other phase 2 and 3 trials have also consistently shown these differences. This review details the putative mechanisms behind the increase in toxic effects, but further work is needed to fully explain the toxic effects differential seen when using the same drug in different cancers. CONCLUSIONS AND RELEVANCE There is a distinct increase in the rate of occurrence of adverse effects of sorafenib when used in differentiated thyroid cancer compared with renal and hepatocellular cancer. While many theoretical explanations have been proposed, the exact mechanism for this differential in toxic effects remains unclear.